This application proposes research into the development of procedures for the preparation of clinical concentrates of human plasma proteins having either existing or potential therapeutic utility. Three proteins have been selected for the primary focus of this research: (1) coagulation factor IX, with the objective of preparing a concentrate devoid of thrombogenic potential; (2) fibronectin, with the objective of developing a method which allows simultaneous recovery of factor VIII; and (3) aplha2-plasmin inhibitor, which may have clinical potential, particularly for replacement therapy in congenital deficiencies. Only those methods which are amenable to large-scale application will be used. These include fractional precipitation with polyethylene glycol, ion exchange chromatography and affinity absorption. Fractions and subfractions generated during the course of large-scale experiments will be used to isolate additional selected plasma proteins, not readily available from other sources, for distribution to investigators outside our organization, in a continued effort to promote studies of their structure and function. These include C1-inactivator, antithrombin III, alpha2-macroglobulin, and alpha1-acid glycoprotein. Furthermore, we will continue to seek collaboration with outside investigators in order to isolate trace components such as angiotensinogen and nonsuppressible insulin-like protein.